Visual field testing (perimetry) is the most widely used method for detecting and monitoring progression of diseases of the optic nerve (i.e. glaucoma, ischemic optic neuropathy, compressive optic neuropathy) and retina. Perimetry is a functional test of the subject's vision. The shape and extent of the defect on the visual field map allows the clinician to confirm the presence of damage, helps to localize where the damage is along the visual pathway (retina, optic nerve, chiasm, optic tract, postgeniculate fibers), and is essential in monitoring progression or improvement over time.
However, perimetry remains a subjective test that requires the subject to make important judgments during the test that can be clouded by anxiety, fatigue, or lack of concentration. A second problem with the current perimetry tests is that almost 40-50% of the optic nerve may be damaged before a significant perceptual change can be detected on the visual field test, making it relatively insensitive for detecting early damage when intervention may still save vision. A third problem is that the visual field test is highly variable in areas of defects where damage has occurred, making it difficult to monitor changes.
New methods are needed to improve the sensitivity for detection of damage and change over time. Objective methods would also provide more reliable determination of the status of the visual system. A number of new technologies have emerged in recent years in an attempt to fill this need and have included multifocal electroretinography (MERG), pattern electroretinography (PERG), visual evoked potential (VEP), multifocal visual evoked potentials (MVEP), and pupil perimetry.
Traditionally, neuronal activity in the central nervous system including the retina has been recorded electrically. Recently however, noninvasive optical recording of neuronal signals from the brain has been demonstrated. Intrinsic changes in the optical properties of active brain tissue (referred to as “intrinsic signals”) permit visualization of neuronal activity when the surface of brain tissue is directly imaged using sensitive CCD cameras. Intrinsic signals refer to the change in the percent reflectance of illuminating (or interrogating) light occurring as a result of the change in the absorption coefficient due to the conversion of oxyhemoglobin to deoxyhemoglobin in response to the metabolic demands of active neurons. The interrogating light is band-restricted to wavelength(s) where the difference in absorption spectra between the oxyhemoglobin and deoxyhemoglobin molecule is the greatest, for example, typically in the region of 580-700 nm. Other sources of the intrinsic signals include changes in the microcirculation and light scattering that are also dependent on neuronal activity.
The intrinsic signals from the brain are usually very small (0.1 to 1.0% of the overall reflected light intensity). However, when appropriately imaged, they can have high spatial resolution (50 microns) corresponding to the areas of active neuronal activity. The small intrinsic signals are isolated from the noise using image subtraction techniques. By subtracting baseline (neuronally less active) images of the brain tissue from stimulated (neuronally active) images, small intrinsic functional signals can be isolated. With the use of optical techniques, it has been possible to record neuronal activities of the primate cortex in vivo.
Visual cortical neurons that are driven preferentially by one eye are grouped into a strip of cortex referred to as an ocular dominance column for that eye. The next strip of cortical cells is driven preferentially by the other eye and forms an adjoining ocular dominance column. These strips of ocular dominance columns alternate between the right and left eye and form a prominent part of the functional architecture of the primate visual cortex. The optical recording of intrinsic signals has allowed the ocular dominance columns to be directly visualized across the cortex in vivo. This was achieved by imaging the cortex with interrogating light, while providing visual stimuli to one eye and then the other. Ocular dominance column images are then constructed by subtracting right eye-stimulated images from the left eye-stimulated images. Optical recording of the temporal lobe of human patients undergoing neurosurgery has also been reported.
Optical recording of the retinal function is noninvasive and ideal for clinical application. The retina is a direct extension of the brain and part of the central nervous system. Neuronal activity of the retina is fundamentally similar to that of the brain. Like the brain, appropriate metabolic changes (changes in hemoglobin oxygen saturation and state of tissue cytochrome for example) can be detected in the retina in response to changes in corresponding reduction of oxyhemoglobin levels. However, the measured changes in reflectance in response to the visual stimulus are on the order of 0.1% to 1.0% of the total reflected intensity level that makes the functional signal difficult to detect by standard methods since it is masked by the other signals (noise) that are present.
What is needed is a practical, non-invasive system and method for revealing retinal function to aid in early detection of retinal and optic nerve diseases such as glaucoma and to monitor for progression of damage. Such a system and method would provide objective, quantitative, and localizing information in the form of a functional image of neuronal-activity across the retina thereby complementing and/or augmenting conventional perimetry. Finally, such a system and method would be instrumental in evaluating animal models of retinal and optic nerve disease and the response to treatment, where perimetry is impractical.